Hitherto we have been considering rather the seat of the operation of medicines, and their manner of reaching it, than the mode in which they produce their effects. The latter point must now receive attention.

1. Mechanical or Physical Methods

The operation of medicines may, in some instances, be purely mechanical or physical. Thus, they may act by excluding the atmospheric air, as in the instance of collodion applied to the skin in cutaneous affections; by mingling with and obtunding the acrimony of various acrid substances, as in the operation of demulcents; by the influence of gravity, as illustrated by the laxative effects of metallic mercury; or by their shape and bulk, as when bran, mustard seed, small shot, etc., operate on the bowels by a mechanical irritation of the mucous membrane.

Endosmose and Exosmose. Another physical mode of action has been suggested, which, though not satisfactorily established, is not without a certain amount of plausibility. Reference has already been made to the entrance of medicines into the blood-vessels on the principle of endosmose. Poiseuille and others have demonstrated that, if the serum of the blood be placed on one side of an animal membrane out of the body, and certain strong saline solutions, or other concentrated liquids on the other side, a current of the serum is made to set through the membrane towards the denser liquid; while, if the solution be very weak, the current is established in a contrary direction. Hence, it has been suggested that strong solutions of certain salts in the stomach and bowels may act as cathartics, by producing an extravasation of the serum from the bloodvessels; while weak solutions of the same may enter the vessels, and thus act on the system generally. This principle has been extensively applied to the explanation of the action of medicines; the general rule being, that a liquid denser than the blood will produce exosmose of the serum, and thus operate as an evacuant.* But the principle is not reconcilable with many facts which might be adduced, and is wholly insufficient to explain many others. To mention only a single example; chloroform taken internally, or applied to the surface of the body, produces effects on the system which can scarcely be referred to any other cause than its presence in the circulation. It must, therefore, enter the blood-vessels, though vastly denser than the serum of the blood, and fails to produce the extravasation, which ought to take place upon the principle of exosmose referred to. Still, this physical property may be received as one of the probable agencies through which medicines operate, though, in the present state of our knowledge, it cannot be admitted as of universal or even general application.

* See experiments of Poiseuille (Comptes Rendus, xix. 944, a.d. 1844), and of Dr. Cogswell (Loud. Med. Times ana Gaz., Jan. 3, 1852, p. 23). See also an essay by Prof. Jos. Carson, on osmosis in its relation to medicine, in the .4m. Journ. of Med.

Sci., July, 1865, p. 135.

The supposed agency of endosmose and exosmose has been carried much further than to the explanation of the action of medicines on exposed surfaces. Thus it may be exerted in the circulation itself, causing the character of the red corpuscles to vary with the varying relative density of the serum without, and the liquid within the corpuscles; so that whatever increases the specific gravity of the serum, as certain salts, for example, shall cause an exosmose of the corpuscular contents, and a shrinking of those bodies, and whatever diminishes its density, as water, shall occasion an endosmose into them, and their consequent distension or rupture.

Still further, it is thought that the relative density of the liquor sanguinis in the capillaries, and of the moisture without them, may be one of the controlling influences in the operation of medicines which act through the circulation. If the nature of the medicine be such as to increase the density of the blood, it would tend to promote absorption from the tissues, if to lessen it, to favour extravasation into them; and the same explanation ought to apply also to the influence of medicines within the circulation upon the various secretions. At present, however, all this is merely hypothesis or conjecture; and must be placed upon the same basis of admissibility with that theory of the operation of medicines. which ascribes it to the mechanical influence of the shape of their ultimate particles upon the tissues with which they come into contact.